Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract, through recent developments in ingestible robotic devices. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems.

Here, inspired by the jetting systems of cephalopods, we developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for both tubular and globular segments of the gastrointestinal tract. These systems are implemented in both tethered and ingestible formats, facilitating endoscopic applications and patient self-dosing.

Our study identified suitable pressure and nozzle dimensions for different segments of the gastrointestinal tract and applied microjets in a variety of devices that support delivery across its various anatomical regions. We characterized the ability of these systems to administer macromolecules, including insulin, a glucagon-like peptide-1 (GLP-1) analogue, and small interfering RNA (siRNA), in large animal models, achieving exposure levels similar to those of subcutaneous delivery.

This research provides key insights into jetting design parameters for gastrointestinal administration, substantially broadening the possibilities for future endoscopic and ingestible drug delivery devices.